Despite behavioral evidence showing placebo modulations of motor performance, the neurophysiological underpinnings of these effects are still unknown. By applying transcranial magnetic stimulation (TMS) over the primary motor cortex, we investigated whether a placebo modulation of force could change the excitability of the corticospinal system. Healthy human volunteers performed a motor task by pressing a piston as strongly as possible with the right index finger. Two experimental groups were instructed that treatment with peripheral low-frequency transcutaneous electrical nerve stimulation (TENS) applied on the first dorsal interosseus would induce force enhancement. One experimental group was conditioned about the effects of TENS with a surreptitious amplification of the visual feedback signaling the force level. The other group, instead, was only verbally influenced, without conditioning. At the end of the instructive placebo procedure, the two experimental groups reached higher levels of force, believed that TENS had been effective and expected to perform better compared with two control groups, who were not influenced about TENS. Moreover, the experimental groups presented enhanced excitability of the corticospinal system in the muscle specifically involved in the task (first dorsal interosseus), as shown by increased amplitude of the motor evoked potentials and decreased duration of the cortical silent period (the latter only in the conditioned group). Crucially, the TMS pulse was delivered when all the subjects exerted the same amount of force, ruling out bottom-up influences. These findings hint at a top-down, cognitive enhancement of corticospinal excitability as a neural signature of placebo modulation of motor performance.
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